We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Utility of Cerebellar Transcranial Magnetic Stimulation in the Neurorehabilitation of Dysphagia After Stroke

This study is not yet open for participant recruitment.
Verified September 2017 by Prof Shaheen Hamdy PhD FRCP, University of Manchester
Sponsor:
ClinicalTrials.gov Identifier:
NCT03274947
First Posted: September 7, 2017
Last Update Posted: September 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Medical Research Council
University of Nottingham
Information provided by (Responsible Party):
Prof Shaheen Hamdy PhD FRCP, University of Manchester
  Purpose

The study is designed to explore the effectiveness of non-invasive cerebellar stimulation to enhance motor plasticity in the cortex after stroke. The investigators have shown that the human cerebellum is strongly activated during the act of swallowing and when stimulated with single TMS pulses can strongly facilitate the corticobulbar projection to the pharynx in humans. More recently the investigators have identified the most relevant frequency of stimulation of the cerebellum that can produce longer term excitation in the human swallowing motor system. The investigators therefore believe that the potential for cerebellar stimulation in improving swallowing is much greater than other methods for two reasons. Firstly, previous work has shown that unlike successful recovery of hand/arm function which relies on restoring activity in the stroke hemisphere, recovery of swallowing function relies on increased excitability in intact projections from the non-stroke hemisphere. The investigators believe that methods that can enhance these undamaged pathways have a greater chance of inducing recovery in the human swallowing system in unilateral stroke. Additionally cerebellar stimulation produces very high levels of corticobulbar excitation it may also have the advantage of improving dysphagia in posterior fossa strokes. Second, the human cerebellum is relatively easy to target and stimulate and has reduced risk of inducing unwanted effects (such as seizures) which as a consequence makes cerebellar stimulation a more pragmatic method for delivering therapeutic neurorehabilitation to dysphagic stroke patients compared to other more complex/riskier methods.

A final factor is that the investigators have developed a "virtual lesion" model of swallowing dysfunction in healthy volunteers which can be reversed quite successfully with other neuro-stimulation protocols. The investigators can therefore use this model to test the effectiveness of cerebellar stimulation protocols (ipsilateral and contralateral cerebellar sites) before choosing the most effective side to apply stimulation in a proof of principle trial/study in a small group of sub-acute dysphagic patients.

The hypotheses are that cerebellar TMS will:

i. Reverse the brain inhibition and behavioural dysfunction following a virtual lesion model of disrupted swallowing in healthy brain (phase 1); ii. Reduce the degree of aspiration in acute dysphagia after a stroke (phase 2).


Condition Intervention
Oropharyngeal Dysphagia Stroke Device: Cerebellar TMS Device: Sham cerebellar TMS

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: An Exploration of the Application of Non-invasive Cerebellar Stimulation in the Neurorehabilitation of Dysphagia After Stroke

Resource links provided by NLM:


Further study details as provided by Prof Shaheen Hamdy PhD FRCP, University of Manchester:

Primary Outcome Measures:
  • Penetration aspiration scores on videofluoroscopy (number of swallows out of 6 that score 3 or more on the penetration aspiration scale) (Hypothesis 2 protocols 1 and 2) [ Time Frame: 1 hour post intervention and 2 weeks post intervention ]
    Penetration aspiration scores on videofluoroscopy (number of swallows out of 6 that score 3 or more on the penetration aspiration scale)


Secondary Outcome Measures:
  • Improvement of: Functional oral ingestion scale (FOIS) and or the dysphagia severity rating scale (DSRS) (Hypothesis 2 protocol 2) [ Time Frame: 2 weeks post intervention ]
    Improvement of: Functional oral ingestion scale (FOIS) and or the dysphagia severity rating scale (DSRS)


Estimated Enrollment: 72
Anticipated Study Start Date: July 2018
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hypothesis 2 Protocol 2 Low dose TMS
Low level cerebellar TMS. Delivered once per day for 3 days.
Device: Cerebellar TMS
Cerebellar transcranial magnetic stimulation
Active Comparator: Hypothesis 2 Protocol 2 High dose TMS
High level cerebellar TMS. Delivered twice per day for 5 days.
Device: Cerebellar TMS
Cerebellar transcranial magnetic stimulation
Sham Comparator: Hypothesis 2 Protocol 2 Sham
Sham cerebellar TMS. Delivered twice a day for 5 days.
Device: Sham cerebellar TMS
Sham cerebellar transcranial magnetic stimulation
Active Comparator: Hypothesis 2 Protocol 1 Cerebellar TMS
Cerebellar TMS at 10Hz, 250 pulses.
Device: Cerebellar TMS
Cerebellar transcranial magnetic stimulation
Sham Comparator: Hypothesis 2 Protocol 1 Sham
Sham cerebellar TMS
Device: Sham cerebellar TMS
Sham cerebellar transcranial magnetic stimulation

Detailed Description:

Protocols:

Hypothesis 1:

Cortical excitability (in both dominant and non-dominant swallowing cortex) to TMS and swallowing behaviour assessed with a swallowing reaction time task will be measured at baseline. Thereafter, the virtual lesion paradigm will be applied to the dominant swallowing projection followed by the cerebellar intervention (10Hz, 250 pulses). Cerebellar stimulation will be applied (in a randomised fashion) on separate occasions to both the contralateral and ipsilateral cerebellar hemispheres, immediately after the virtual lesion. The investigators have found that placement using known reference landmarks are equivalent to using neuronavigation, so the latter will not be employed. Repeat measurements of cortical excitability and swallowing behaviour will then be performed and analysed against baseline data and a sham cerebellar paradigm. Differences in cortical excitability and swallowing responses will thus be an indication of which cerebellar region (contralesional/ipsilesional) can influence excitability and reverse any behavioural changes most effectively.

Hypothesis 2:

I. Dysphagic stroke patients (n=24) recruited over a 9 month period within 14 days of stroke ictus will have their swallowing assessed by videofluoroscopy before and after receiving either the real or sham cerebellar stimulation (10Hz, 250 pulses) as determined from phase 1. As before, placement of the coil for cerebellar stimulation will be performed using landmarks already established and validated in the work from question 1. Patients will be intubated with the pharyngeal EMG catheter for pre and post recordings of pharyngeal motor evoked potentials (MEPs) to cortical TMS. Power calculations, based on a similar study of pharyngeal stimulation indicated that the investigators would need 12 patients per group to achieve a statistical power of 80% at a 5% significance level to detect changes in the primary outcome measure of aspiration. In this study, the investigators will examine if the chosen site of cerebellar stimulation from phase 1 can induce short-term changes in brain function (pharyngeal MEPs) and swallowing function (videofluoroscopy) compared to sham interventions and baseline measurement, up to 1 hour after the intervention.

II. Following stage I, once it is established that cerebellar stimulation can alter brain and swallowing functions in stroke in the short-term, it will need to be appraised for clinical feasibility, dose response, and longer term efficacy. Dysphagic stroke patients (n=48, 16 patients per group) admitted to the stroke unit and identified by videofluoroscopy will be recruited over the next 21 months. Since it is not known how the cerebellar stimulation method should be delivered to patients, a dose ranging treatment trial will be utilised, randomising patients to one of three groups (A-C), low level stimulation, high level stimulation and sham stimulation. From our previous work with pharyngeal stimulation, the investigators propose that group A will receive stimulation once per day for 3 days. Group B will receive stimulation twice per day for 5 days. Group C will receive sham stimulation (delivered as in protocol I) twice a day for 5 days. Groups A and B will receive stimulation at the optimal site (10Hz, 250 pulses) found in question 1, but all groups will also receive standard speech and language therapy.

Assessments:

Swallowing before and after stimulation will be evaluated using videofluoroscopy, at 1 hour for protocol I. For protocol II the investigators propose both videofluoroscopy and functional scores (Functional oral ingestion scale (FOIS), the dysphagia severity rating scale (DSRS) including feeding status and modified rankin scale (mRS)) at baseline and at 2 weeks.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients aged 18 years and over
  • All patients with an acute anterior or posterior cerebral circulation stroke within 6 weeks of symptom onset.

Exclusion Criteria:

  • Advanced dementia
  • Previous history of dysphagia
  • Patients judged to be clinically unstable
  • Presence of implanted cardiac pacemaker or defibrillator
  • Any severe chronic medical condition that compromises cardiac or respiratory status
  • Patients with acute lower respiratory tract infections requiring antibiotic treatment.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03274947


Contacts
Contact: Shaheen Hamdy, MBChB, PhD +441612064363 shaheen.hamdy@manchester.ac.uk
Contact: Ayodele Dr Sasegbon, MBChB +447944622914 ayodele.sasegbon@manchester.ac.uk

Sponsors and Collaborators
University of Manchester
Medical Research Council
University of Nottingham
Investigators
Principal Investigator: Shaheen Hamdy, MBChB, PhD University of Manchester
  More Information

Publications:

Responsible Party: Prof Shaheen Hamdy PhD FRCP, Professor, University of Manchester
ClinicalTrials.gov Identifier: NCT03274947     History of Changes
Other Study ID Numbers: 5111 protocol ver1
First Submitted: August 14, 2017
First Posted: September 7, 2017
Last Update Posted: September 7, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No identifiable individual participant information will be shared outside the immediate research team. However, identifiable individual participant information will be made available to the Medical research council and the University of Manchester if required for the purposes of auditing the study.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Prof Shaheen Hamdy PhD FRCP, University of Manchester:
Oropharyngeal Dysphagia
Stroke

Additional relevant MeSH terms:
Stroke
Deglutition Disorders
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Pharyngeal Diseases
Otorhinolaryngologic Diseases